当归对兔肝纤维化肝癌介入治疗后肝纤维化的作用

目的 建立兔肝纤维化肝癌模型,观察当归对其行化疗栓塞(TACE)术后加重肝纤维化的预防作用,探讨当归预防肝纤维化的作用机制.方法 将55只新西兰大白兔随机表法分为对照组(n=10)、模型组(n=15)、介入组(n=15)和预防组(n=15).造模时给予腹腔注射纯CCl4剂量0.1 ml/kg,每周1次,共注射10周,同时给予5%的乙醇饮水,在第10周末于肝左叶种植VX2瘤.其中模型组:在第12周末经肝动脉注入生理盐水2ml;介入组:在行TACE术时注入平阳霉素1mg+碘油0.2ml;预防组:在行TACE术时注入平阳霉素1mg+碘油0.2ml+当归注射液6ml/kg.对照组:以相同剂量生理盐水注射.各组于第16周末检测透明质酸酶(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(CⅣ),并进行肝组织苏木素咿红(HE)染色、胶原纤维(VG)染色和转化生长因子(TGF)-β1免疫组织化学染色.结果 模型组(7/10)和预防组(6/10)的肝纤维化病理分期主要处于肝纤维化Ⅱ期(P>0.05),介入组(7/9)主要处于肝纤维化Ⅲ期,与模型组(3/10)和预防组(4/10)分期比较差异有统计学意义(P<0.05);模型组、介入组和预防组血清HA、LN、PCⅢ和CⅣ明显高于对照组(P<0.05),预防组低于介入组(P<0.05),与模型组比较差异无统计学意义(P>0.05);对照组肝组织TGF-β1呈阴性表达,介入组肝组织TGF-β1表达明显增强,模型组和预防组TGF-β1表达较介入组减少.结论 用CCl4诱发兔肝纤维化后并种植VX2瘤,可以建立兔肝纤维化肝癌模型,行TACE术后可加重其肝纤维化的程度,当归对其有延缓作用,TGF-β1参与其调控机制.

Effect of Angelica Sinensis on the rabbits model of hepatic fibrosis combined with hepatic carcinoma after transarterial chemoembolization

Objective To establish an animal model of hepatic fibrosis combined with hepatic carcinoma in New Zealand white rabbits, to evaluate preventive effect of Angelica Sinensis on hepatic fibrosis after transarterial chemoembolization (TACE) , and to investigate the mechanism of anti-hepatic fibrosis. Methods Fifty-five New Zealand white rabbits were divided randomly into four groups: model group (n= 15) was created by intraperitoneal injection of 100% carbon tetrachloride ( CCl4) (0.1 ml/kg once a week) along with edible ethanol for ten weeks, then VX2 tumors were transplanted in the left lobe of the liver at the end of 10th week and saline (2 ml) was given by hepatic artery at the end of 12th week; Intervention group (n=15) was given pingyangmycin (1 mg) and iodized oil (0. 2 ml) by TACE; Prevention group (n=15) was given pingyangmycin (1 mg) , iodized oil (0. 2 ml) and Angelica Sinensis (6 ml/kg) by TACE; Control group (n=10) was created with the same dose of injection of saline. Serum levels of hyaluronic acid ( HA) ,laminin ( LN) , procollagen type Ⅲ ( PC Ⅲ) , collagen type Ⅳ(C Ⅳ ) and liver specimens were obtained at the end of 16th week. The histological changes were examined by HE, VG staining and transforming growth factor (TGF)-pl immunohistochemistry staining. Results Hepatic fibrosis in the model group and the prevention group was mostly in stages II , and that in the intervention group was mostly in stages M. There was significant difference between the intervention group and the model group or the prevention group (P<0. 05). Serum HA, LN, PC Ⅲ and CIV levels in the model group, the intervention group and the prevention group were higher than thsoe in the control group (P < 0.05), and those in the prevention group were lower than those in the intervention group ( P < 0. 05 ) , but there was no significant difference between the prevention group and the model group (P > 0. 05). The TGF-βl expression in the prevention group was significantly reducerd as compared with that in the model group (P<0.05 ).Conclusion The model of hepatic fibrosis combined with hepatic carcinoma in rabbits was successfully made by intraperitoneal injection of 100% CCl4. Angelica Sinensis injection can inhibit hepatic fibrosis after TACE in the rabbit model of hepatic fibrosis combined with VX2 tumor, and the mechanism of anti-hepatic fibrosis might possibly be associated with down-regulation of TGF-pl.